A team of scientists at Emory and Georgia Tech
has found a genetic link between mechanical changes in blood flow
patterns and the development of atherosclerotic plaques.
The discovery could help explain how increasing blood
flow through physical activity helps prevent atherosclerosis.
Hanjoong Jo, a professor in the two schools’ joint Wallace
H. Coulter Department of Biomedical Engineering, and his colleagues
used a combined engineering and molecular approach to demonstrate
how changes in blood flow might contribute to the prevention or
development of lipid-containing plaques that can rupture and block
blood vessels, leading to heart attack and stroke. The research
is published in the online edition of the Journal of Biological
Bioengineers believe that areas of the vascular system with curves,
forks and less direct flow are more likely to develop atherosclerotic
plaques than areas with straight and unobstructed blood flow. Jo
hypothesized that endothelial cells (which line blood vessels) have
a biological response to alterations in their mechanical environment.
Using a test fluid, he designed a mechanical system to model the
patterns made by blood as it flows through the body’s vessels,
and then exposed the fluid to aortic endothelial cells of mice.
Through microarray (gene chip) technology, Jo screened 12,000 genes
found in the endothelial cells, comparing tissue exposed to a straight
and streamlined flow of blood (laminar shear) to tissue exposed
to abnormal, non-linear flow patterns (oscillatory shear stress).
In the cells exposed to oscillatory shear stress, he discovered
a marked increase in expression of the gene that encodes the protein
BMP4 (bone-morphogenetic protein-4). In the cells exposed to laminar
shear, he found almost no evidence of BMP4.
To further support his results, Jo’s team, in collaboration
with Emory cardiologist Robert Taylor and vascular surgeon David
Vega, screened endothelial cells from human coronary arteries of
patients with atherosclerotic lesions to test for expression of
BMP4. BMP4 expression was undetectable in arteries with minimal
disease, but it was strongly expressed in endothelial patches found
overlying an early form of atherosclerotic lesions called “foam
Although high blood cholesterol, high blood pressure, smoking and
a diet high in saturated fat are known to increase the likelihood
of developing heart disease, the risk of physical inactivity is
comparable to other factors, according to the American Heart Association.
“The molecular biological response to increases or decreases
in blood flow might help us explain why physical inactivity promotes
disease,” Jo said. “Increasing one’s heart rate
through vigorous exercise causes blood to flow faster through the
vessels, and some exercise-related benefits may be due to endothelial
expression of certain genes and proteins.”
Jo hopes to use his findings about BMP4 to develop new diagnostic
tests or gene-based therapies to prevent plaque formation.
In addition to Taylor and Vega, Jo’s research team of biomedical
engineers, cardiologists and surgeons included George Sorescu, Michelle
Sykes, Daiana Weiss, Manu Platt, Aniket Saha, Jinah Hwang, Nolan
Boyd and Yong Boo.